Time for sleep to take the stage?

In the preclinical stages of Alzheimer’s Disease (AD), prior to cognitive impairment, poor sleep quality is associated with amyloid deposition. The finding comes from a cross-sectional study of volunteers from the Washington University Knight Alzheimer’s Research Center. Half of those studied had a history of late-onset AD in their parents; and all were older than sixty years. 

Such a correlation does not imply causality, of course; but there is now evidence that the links between AD and poor sleep are bidirectional. 

Insufficient sleep has not featured prominently among the lifestyle factors associated with risk of dementia. According to Sebastiaan Overeem, of the Sleep Medicine Centre of the Eindhoven University of Technology, the Netherlands, a growing body of animal and human data suggest this should change, since disturbed sleep relates to the dynamics of amyloid-beta. 

In transgenic mice, sleep deprivation increases deposition of amyloid plaque in several cortical areas. In healthy subjects, sleep loss attenuates the normal circadian rhythm in amyloid beta levels in the CSF. In particular, the reduction which normally occurs during sleep is less apparent. 

Sleep may be a modifiable risk factor for AD

Sleep pathology, brain pathology

In established AD, severe sleep pathology and circadian rhythm disturbance is seen in up to 40% of patients. The clearest abnormality is a decrease in REM sleep: periods of REM are shorter and there is less total time spent in this sleep state. Overall, sleep is fragmented and interrupted by long periods of wakefulness. This contributes to agitation and confusion, and results in daytime somnolence. In some AD patients, there is virtual reversal of the sleep-wake cycle. 

This diminishes the quality of life of patients and caregivers and is one of the most important reasons for transfer to an institution. Sleep disruption in AD is also associated with reduced survival. Part of the reason may be AD-related atrophy of the suprachiasmatic nucleus. Also, post mortem studies show that -- compared with controls -- there is a decrease in sleep-related orexin/hypocretin neurons in the hypothalamus.

The brain likes winning

These insights into sleep and AD came during a workshop which also considered the role of sleep in healthy functioning, particularly in relation to memory. Sleep, particularly the slow-wave phase, is associated with a dialogue between the ventral striatum and hippocampus. This conversation seems involved in the off-line consolidation of memory, and perhaps especially of memories with emotional salience. The process is disrupted by sleep deprivation. 

Virginie Sterpenich, University Hospitals, Geneva, Switzerland, described an ingenious experiment which investigated the relationship between emotion and memory. 

Healthy subjects played two games – one involving face recognition and the other navigating a maze. The two tasks were chosen because the brain areas involved are quite different. Unknown to the subjects, the experimenter controlled the contingencies of the games such that one would be won and the other inevitably lost. Subjects then slept while EEG and functional MRI were used to monitor brain activity. 

During deep sleep, subjects who had won the face recognition game showed greater activity in the brain areas related to this task; and those who had won the maze game showed greater activity in areas related to the spatial task. The conclusion: the brain is selective in the way it consolidates memory. 

Dr Sterpenich also presented data from a study in which volunteers kept dream diaries and were studied while engaging with emotionally salient or neutral items on the following day. Subjects with greater emotional content in their dreams of the night before showed greater activity in brain regions involved with the regulation of emotion.